scholarly journals Blood-Brain Barrier: Real-time Feedback-controlled Focused Ultrasound Disruption by Using an Acoustic Emissions–based Controller

Radiology ◽  
2012 ◽  
Vol 263 (1) ◽  
pp. 96-106 ◽  
Author(s):  
Meaghan A. O’Reilly ◽  
Kullervo Hynynen
Keyword(s):  
Real Time ◽  
Blood Brain Barrier ◽  
Focused Ultrasound ◽  
Acoustic Emissions ◽  
Brain Barrier ◽  
Blood Brain

Localized blood–brain barrier opening in infiltrating gliomas with MRI-guided acoustic emissions–controlled focused ultrasound

2021 ◽  
Vol 118 (37) ◽  
pp. e2103280118
Author(s):  
Pavlos Anastasiadis ◽  
Dheeraj Gandhi ◽  
Yutong Guo ◽  
Abdul-Kareem Ahmed ◽  
Soren M. Bentzen ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Focused Ultrasound ◽  
Acoustic Emissions ◽  
Fold Increase ◽  
Brain Barrier ◽  
Vascular Density ◽  
Blood Brain ◽  
Order Of Magnitude ◽  
Mri Guided ◽  
Bbb Opening

Pharmacological treatment of gliomas and other brain-infiltrating tumors remains challenging due to limited delivery of most therapeutics across the blood–brain barrier (BBB). Transcranial MRI-guided focused ultrasound (FUS), an emerging technology for noninvasive brain treatments, enables transient opening of the BBB through acoustic activation of circulating microbubbles. Here, we evaluate the safety and utility of transcranial microbubble-enhanced FUS (MB-FUS) for spatially targeted BBB opening in patients with infiltrating gliomas. In this Phase 0 clinical trial (NCT03322813), we conducted comparative and quantitative analyses of FUS exposures (sonications) and their effects on gliomas using MRI, histopathology, microbubble acoustic emissions (harmonic dose [HD]), and fluorescence-guided surgery metrics. Contrast-enhanced MRI and histopathology indicated safe and reproducible BBB opening in all patients. These observations occurred using a power cycling closed feedback loop controller, with the power varying by nearly an order of magnitude on average. This range underscores the need for monitoring and titrating the exposure on a patient-by-patient basis. We found a positive correlation between microbubble acoustic emissions (HD) and MR-evident BBB opening (P = 0.07) and associated interstitial changes (P < 0.01), demonstrating the unique capability to titrate the MB-FUS effects in gliomas. Importantly, we identified a 2.2-fold increase of fluorescein accumulation in MB-FUS–treated compared to untreated nonenhancing tumor tissues (P < 0.01) while accounting for vascular density. Collectively, this study demonstrates the capabilities of MB-FUS for safe, localized, controlled BBB opening and highlights the potential of this technology to improve the surgical and pharmacologic treatment of brain tumors.

scholarly journals Cavitation dose painting for focused ultrasound-induced blood-brain barrier disruption

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yaoheng Yang ◽  
Xiaohui Zhang ◽  
Dezhuang Ye ◽  
Richard Laforest ◽  
Jeffrey Williamson ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Focused Ultrasound ◽  
Brain Barrier ◽  
Dose Painting ◽  
Barrier Disruption ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
Brain Barrier Disruption

scholarly journals DDEL-13. FOCUSED ULTRASOUND MEDIATED BLOOD BRAIN BARRIER DISRUPTION IN A MURINE MODEL OF PONTINE GLIOMA: A SAFETY AND FEASIBILITY STUDY

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii286-iii286
Author(s):  
Zachary Englander ◽  
Hong-Jian Wei ◽  
Antonios Pouliopoulos ◽  
Pavan Upadhyayula ◽  
Chia-Ing Jan ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Focused Ultrasound ◽  
Brain Barrier ◽  
Center Frequency ◽  
Single Element ◽  
Pontine Glioma ◽  
Orthotopic Model ◽  
Function Generator ◽  
Blood Brain ◽  
Glioma Model

Abstract BACKGROUND Drug delivery remains a major obstacle in DIPG, as the blood brain barrier (BBB) limits the penetration of systemic therapies to the brainstem. Focused ultrasound (FUS) is an exciting new technology that, when combined with microbubbles, can open the BBB permitting the entry of drugs across the cerebrovasculature. Given that the utility of FUS in brainstem tumors remains unknown, the purpose of our study was to determine the safety and feasibility of this technique in a murine pontine glioma model. METHODS A syngeneic orthotopic model was established by stereotactic injection of PDGF-B+PTEN-/-p53-/- murine glioma cells (10,000/1ul) into the pons of B6 albino mice. A single-element, spherical-segment FUS transducer (center frequency=1.5MHz) driven by a function generator through a power amplifier (acoustic pressure=0.7MPa) was used with concurrent intravenous microbubble injection (FUS+MB) to sonicate the tumor on post-injection day 14. BBB opening was confirmed with gadolinium-enhanced MRI and Evans blue. Kondziela inverted screen (KIS) testing was completed to measure motor function. Mice were either immediately sacrificed for histopathological assessment or serially monitored for survival. RESULTS In mice treated with FUS (n=11), there was no measured deficit in KIS testing. Additionally, the degree of intra-tumoral hemorrhage and inflammation on H&E in control (n=5) and treated mice (n=5) was similar. Lastly, there was no difference in survival between the groups (control, n=6, median=26 days; FUS, n=6, median=25 days, p&gt;0.05). CONCLUSION FUS+MB is a safe and feasible technique to open the BBB in a preclinical pontine glioma model.

scholarly journals Contrast-Enhanced Ultrasound Imaging for the Detection of Focused Ultrasound-Induced Blood-Brain Barrier Opening

Theranostics ◽  
2014 ◽  
Vol 4 (10) ◽  
pp. 1014-1025 ◽  
Author(s):  
Ching-Hsiang Fan ◽  
Wun-Hao Lin ◽  
Chien-Yu Ting ◽  
Wen-Yen Chai ◽  
Tzu-Chen Yen ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Ultrasound Imaging ◽  
Focused Ultrasound ◽  
Brain Barrier ◽  
Contrast Enhanced Ultrasound ◽  
Blood Brain ◽  
Contrast Enhanced ◽  
Barrier Opening ◽  
Blood Brain Barrier Opening

scholarly journals Safety evaluation of a clinical focused ultrasound system for neuronavigation guided blood-brain barrier opening in non-human primates

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Antonios N. Pouliopoulos ◽  
Nancy Kwon ◽  
Greg Jensen ◽  
Anna Meaney ◽  
Yusuke Niimi ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Safety Profile ◽  
Focused Ultrasound ◽  
Multiple Case Study ◽  
Brain Barrier ◽  
Non Invasive ◽  
Blood Brain ◽  
Multiple Case ◽  
Bbb Opening

AbstractAn emerging approach with potential in improving the treatment of neurodegenerative diseases and brain tumors is the use of focused ultrasound (FUS) to bypass the blood–brain barrier (BBB) in a non-invasive and localized manner. A large body of pre-clinical work has paved the way for the gradual clinical implementation of FUS-induced BBB opening. Even though the safety profile of FUS treatments in rodents has been extensively studied, the histological and behavioral effects of clinically relevant BBB opening in large animals are relatively understudied. Here, we examine the histological and behavioral safety profile following localized BBB opening in non-human primates (NHPs), using a neuronavigation-guided clinical system prototype. We show that FUS treatment triggers a short-lived immune response within the targeted region without exacerbating the touch accuracy or reaction time in visual-motor cognitive tasks. Our experiments were designed using a multiple-case-study approach, in order to maximize the acquired data and support translation of the FUS system into human studies. Four NHPs underwent a single session of FUS-mediated BBB opening in the prefrontal cortex. Two NHPs were treated bilaterally at different pressures, sacrificed on day 2 and 18 post-FUS, respectively, and their brains were histologically processed. In separate experiments, two NHPs that were earlier trained in a behavioral task were exposed to FUS unilaterally, and their performance was tracked for at least 3 weeks after BBB opening. An increased microglia density around blood vessels was detected on day 2, but was resolved by day 18. We also detected signs of enhanced immature neuron presence within areas that underwent BBB opening, compared to regions with an intact BBB, confirming previous rodent studies. Logistic regression analysis showed that the NHP cognitive performance did not deteriorate following BBB opening. These preliminary results demonstrate that neuronavigation-guided FUS with a single-element transducer is a non-invasive method capable of reversibly opening the BBB, without substantial histological or behavioral impact in an animal model closely resembling humans. Future work should confirm the observations of this multiple-case-study work across animals, species and tasks.

Sign in / Sign up

Export Citation Format

Share Document